大鼠心脏二价金属转运体1表达量的不同发育期变化及其调节

目的：研究二价金属转运体1(divalent metal transporterl，DMTl)在大鼠心脏中的表达及其受膳食铁调节的情况。方法：采用RT—PCR和Western blot技术，观察DMTl在雄性Sprague—Dawley大鼠心脏中的表达。结果：两种亚型的DMTl mRNA(non—IRE形式和IRE形式)在不同年龄(7、21、63和196d)的大鼠心脏中均有表达，随着大鼠年龄的增加，DMTl mRNA的表达量增加，并又其表达量与心脏中的铁合量呈正相关。出生21d的大鼠用高铁或低铁饲料喂养6周后，分别造成心脏铁超载和铁缺乏模型。高铁组、低铁组与对照组相比，心脏DMTl mRNA的表达量没有明显变化；Western blot分析结果显示，DMTl蛋白(non—IRE形式和IRE形式)在铁缺乏的心脏中合量分别增加21％和40％(P＜0．01)，在铁超载的心脏中其合量降低26％～28％(P＜0．01)。结论：DMTl在心脏中的表达受膳食铁和心脏铁合量的调节，其调节方式与转铁蛋白受体不同，是一种转录后调节。     

载体定量杀菌试验检测臭氧消毒效果的改进研究

目的 改进载体定量杀菌试验的试验方法,以提高臭氧消毒效果的检测效率。方法 以大肠杆菌（Escherichia coli)8099作为指示微生物,以玻片为载体进行载体定量杀菌试验,分别对干燥处理与未干燥处理的染菌载片进行消毒效果检测。结果 在臭氧浓度为6.94 mg/L、压强为50 kPa的条件下,作用50 s后,未干燥处理的菌片杀灭率高达100%,平均杀灭对数值为（5.97±0.06）,平均存活率对数值为（-5.97±0.06）;干燥处理的菌片平均杀灭率只有（60.49±12.70）%,平均杀灭对数值为（0.42±0.13）,平均存活率对数值为（-0.42±0.13）,2种处理方法检测出的臭氧消毒效果差异具有统计学意义（P＜0.05）。结论 相比干燥处理,采用未干燥处理的染菌载片进行臭氧消毒效果的检测,方法操作简单、效率更高、效果更好。     

醋白芍、炙甘草及其配伍载体中药效组分变化规律分析

目的:研究醋白芍、炙甘草及其配伍载体中醋白芍及炙甘草药效组分的变化规律。方法:以醋白芍、炙甘草单味药及其药对为研究对象,采用水煎煮法制备供试品溶液,采用HPLC法测定。结果:醋白芍4种药效组分(氧化芍药苷、芍药内酯苷、芍药苷、苯甲酰芍药苷)含量分别为:醋白芍(1.07±0.12、0.36±0.02、2.00±0.21、0.37±0.03)mg/m L;醋白芍-甘草(1.89±0.11、0.86±0.05、3.25±0.13、0.52±0.03)mg/m L;醋白芍-炙甘草(1.90±0.09、0.87±0.04、3.30±0.24、0.52±0.01)mg/m L。炙甘草五种药效组分(甘草酸、甘草苷、甘草素、异甘草苷、异甘草素)含量分别为:炙甘草(6.53±0.25、2.17±0.33、0.52±0.21、0.48±0.23、0.09±0.03、9.79±0.65)mg/m L;炙甘草-焦白芍(5.13±0.32、2.11±0.21、0.47±0.12、0.57±0.22、0.12±0.02、8.40±0.75)mg/m L;炙甘草-炒白芍(6.47±0.33、2.67±0.23、0.56±0.23、0.60±0.23、0.12±0.01、10.42±0.78)mg/m L;炙甘草-醋白芍(8.76±0.35、3.10±0.43、0.79±0.32、0.76±0.34、0.15±0.05、13.56±0.99)mg/m L。结论:配伍影响或改变了药效组分的物理、化学性质,进而改变了药效组分的溶出,最终改变了药效组分在复方汤剂中存在状态。中药治疗作用的关键在于药效组分,包括药效组分的组成及各药效组分之间的比例。药效组分的组成不同,疗效也不同;药效组分的组成相同,但比例不同,疗效也不一样。不同组成的药效组分或不同比例的药效组分分别代表不同的中药,具有不同的临床疗效,其根源在于药效组分的不同,应加以区分。因此,对中药药效组分的研究与探讨是解析中药配伍机制的关键。     

Raising obstetricians’ awareness of spinal muscular atrophy: towards early detection and reproductive planning

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that is caused by degeneration of α motor neurons in the spinal cord anterior horns. This degeneration can lead to progressive atrophy of proximal muscles, weakness, respiratory failure and death in severe cases. SMA is the most common neuromuscular disease of childhood and one of the main causes of infant death, with no cure in sight. This review highlights the impact of the disease in families, summarizes genetics and ultrasound advances, discusses how obstetricians can work towards its early detection and explores the options for reproductive planning.     

STR遗传标记在广西地区血友病A携带者诊断中的应用

目的：建立理想的STR遗传标记体系,对广西地区血友病A携带者进行快速简便的基因诊断。方法：选取广西地区10个血友病A家系作为研究对象,运用荧光PCR联合毛细管电泳的方法,对家系成员中FⅧ基因内外具有高度遗传性的3个STR位点F8Int13、DXS1073、DXS9901进行等位基因分型,评估该体系用于家系中血友病A携带者的诊断效率,并对待检者进行携带者诊查。结果：10个血友病A家系中,11例肯定女性携带者均含有与相应先证者完全一致的3个STR等位基因（F8Int13、DXS1073、DXS9901）片段长度;在待检的8例女性中,5例检出3个STR等位基因片段与相应家系中先证者完全相同,被诊断为血友病A携带者。结论：联合应用3个STR位点F8Int13、DXS1073、DXS9901进行遗传分析能够快速检出血友病A携带者,给血友病A产前诊断提供可靠的依据。     

A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes

Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.     

新型外用药物贮库TPR凝胶的初步研究

热塑型橡胶(Thermoplastic Rubber),简称TPR,俗称人造橡胶。本实验采用SBS、抗氧化剂1010、液体石蜡(15#)、145树脂等为原料配制TPR凝胶,用直接混合法制备了含樟脑的TPR凝胶贴剂,并经乙醇浸出后用GC检测了樟脑含量。实验结果表明:TPR凝胶可作为挥发油类药物贮库,其内含的挥发油成分可在乙醇中释放,其释放量与时间有明显相关性。本实验具有一定的理论和实用价值,为TPR凝胶作为外用贴敷类药物载体的应用做了探索性工作。     

Maternal carrier screening with single-gene NIPS provides accurate fetal risk assessments for recessive conditions

PurposeThe purpose of this study was to evaluate the clinical performance of carrier screening for cystic fibrosis, hemoglobinopathies, and spinal muscular atrophy with reflex single-gene noninvasive prenatal screening (sgNIPS), which does not require paternal carrier screening.MethodsAn unselected sample of 9151 pregnant individuals from the general US pregnant population was screened for carrier status, of which 1669 (18.2%) were identified as heterozygous for one or more pathogenic variants and reflexed to sgNIPS. sgNIPS results were compared with newborn outcomes obtained from parent survey responses or provider reports for a cohort of 201 pregnancies.ResultsOverall, 98.7% of pregnant individuals received an informative result (no-call rate = 1.3%), either a negative carrier report or, if identified as heterozygous for a pathogenic variant, a reflex sgNIPS report. In the outcomes cohort, the negative predictive value of sgNIPS was 99.4% (95% CI = 96.0%-99.9%) and average positive predictive value (PPV) of sgNIPS was 48.3% (95% CI = 36.1%-60.1%). Importantly, personalized PPVs accurately reflected the percentage of affected pregnancies in each PPV range, and all pregnancies with a sgNIPS fetal risk of >9 in 10 (90% PPV) were affected.ConclusionAlthough traditional carrier screening is most effective when used to assess reproductive risk before pregnancy, more than 95% of the time it is pursued during a pregnancy and is complicated by incomplete uptake of paternal carrier screening (<50%) and misattributed paternity (～10%). Even in an idealized setting, when both partners have carrier screening, the maximum risk for having an affected pregnancy is 1 in 4 (equivalent of a 25% PPV). Carrier screening with sgNIPS during pregnancy is an alternative that does not require a paternal sample and provides accurate fetal risk in a timely manner that can be used for prenatal counseling and pregnancy management.     

Incidental molecular diagnoses and heterozygous risk alleles in a carrier screening cohort

PurposeExpanded pan-ethnic carrier screening is an effective tool for the management of reproductive risk. However, growth in the number of conditions screened, in combination with increasingly more comprehensive test methodologies, can lead to the detection of genetic findings that may affect the health of the tested individual. The objective of this study was to investigate the frequency of pathogenic genotypes in a presumed healthy carrier screening cohort to facilitate broader discussions regarding disclosure of genetic information from carrier screening.MethodsA retrospective analysis of 73,755 targeted carrier screens was performed to identify individuals with pathogenic genotypes and heterozygous risk alleles.ResultsIn this study, we identified 79 individuals (0.11%) with pathogenic genotypes associated with moderate to profound autosomal recessive or X-linked conditions. In addition, 10 cases had chromosome X dosage abnormalities suggestive of a sex chromosome abnormality. Heterozygote risk alleles represented the majority of ancillary findings in this cohort, including 280 female carriers of FMR1 premutation alleles, 15 heterozygous females with pathogenic DMD variants, and 174 heterozygotes with pathogenic variants in genes that may confer increased risk for somatic malignancies in the heterozygous state.ConclusionThese data suggest that nearly 1% of individuals undergoing carrier screening will have a finding that may require clinical evaluation or surveillance.